Treatment planning for brachytherapy: an integer programming model, two computational approaches and experiments with permanent prostate implant planning

An integer linear programming model is proposed as a framework for optimizing seed placement and dose distribution in brachytherapy treatment planning. The basic model involves using 0/1 indicator variables to describe the placement or non-placement of seeds in a prespecified three-dimensional grid of potential locations. The dose delivered to each point in a discretized representation of the diseased organ and neighbouring healthy tissue can then be modelled as a linear combination of the indicator variables. A system of linear constraints is imposed to attempt to keep the dose level at each point to within specified target bounds. Since it is physically impossible to satisfy all constraints simultaneously, each constraint uses a variable to either record when the target dose level is achieved, or to record the deviation from the desired level. These additional variables are embedded into an objective function to be optimized. Variations on this model are discussed and two computational approaches--a branch-and-bound algorithm and a genetic algorithm--for finding 'optimal' seed placements are described. Results of computational experiments on a collection of prostate cancer cases are reported. The results indicate that both optimization algorithms are capable of producing good solutions within 5 to 15 min, and that small variations in model parameters can have a measurable effect on the dose distribution of the resulting plans.     

The effect of allergen immunotherapy on in vitro IL-4 and IFN-gamma production by peripheral mononuclear cells in house dust-sensitive Chinese patients with bronchial asthma

The IFN-gamma produced by Th1 cells and IL-4 produced by Th2 cells are two most important cytokines in the regulation of IgE production. House dust immunotherapy has been tried in the treatment of house dust-sensitive Chinese asthmatic patients with good results. We examined the influence of such treatment on in vitro IL-4 and IFN-gamma production by peripheral blood mononuclear cells in house dust-sensitive asthmatic patients. Allergen immunotherapy in house-dust sensitive asthmatic patients can significantly decrease IL-4 production from peripheral mononuclear cells (p<0.05). The production levels of IL-4 in patients without treatment had higher levels than those in patients with hyposensitization (p<0.01). Such therapy also have some effect on promotion of IFN-gamma production in asthmatic patients. In conclusion, immunotherapy with house dust may have the potential ability to shift the Th1/Th2 balance of immune response to allergens and to create a favorable cytokine microenvironment to suppress the allergic reaction in the asthmatic airway.     

Biaxial mechanical/structural effects of equibiaxial strain during crosslinking of bovine pericardial xenograft materials

We have investigated the effect of biaxial constraint during glutaraldehyde crosslinking on the equibiaxial mechanical properties of bovine pericardium. Crosslinking of cruciate samples was carried out with: (i) no applied load, (ii) an initial 25 g ( approximately 30 kPa) equibiaxial load, or (iii) an initial 200 g (approximately 250 kPa) equibiaxial load. All loading during crosslinking was done under a defined initial equibiaxial load and subsequently fixed biaxial strain. Load changes during crosslinking were monitored. Mechanical testing and constraint during crosslinking were carried out in a custom-built biaxial servo-hydraulic testing system incorporating four actuators with phase-controlled waveform synthesis, high frame-rate video dimension analysis, and computer-interfaced data acquisition. The paired biaxial stress strain responses under equibiaxial loading at 1 Hz (before and after treatment) were evaluated for changes in anisotropic extensibility by calculation of an anisotropy index. Scanning electron microscopy (SEM) was performed on freeze-fractured samples to relate collagen crimp morphology to constraint during crosslinking. Fresh tissue was markedly anisotropic with the base-to-apex direction of the pericardium being less extensible and stiffer than the circumferential direction. After unconstrained crosslinking, the extensibility in the circumferential direction, the stiffness in the base-to-apex direction, and the tissue's anisotropy were all reduced. Anisotropy was preserved in the tissue treated with an applied 25 g load; however, tissue treated with an applied 200 g load became extremely stiff and nearly isotropic. SEM micrographs correlated well with observed extensibility in that the collagen fibre morphology changed from very crimped (unconstrained crosslinking), to straight (200 g applied load). Biaxial stress-fixation may allow engineering of bioprosthetic materials for specific medical applications.     

Laparoscopically assisted full thickness skin graft for reconstruction in congenital agenesis of vagina and uterine cervix

In patients with agenesis of the vagina and cervix but with a functional endometrium, the traditional treatment is hysterectomy with construction of a neovagina. We report successful treatment by laparoscopically assisted full thickness skin graft for reconstruction in a patient with congenital agenesis of the vagina and uterine cervix concomitant with haematometra and ovarian endometrioma in a 12 year old girl. Postoperatively, the vaginal skin graft healed well, and menstruation first appeared 4 weeks later. In our opinion, a combined laparoscopic and vaginal procedure with full thickness skin graft is an efficacious alternative in managing such genital defects.     

Production and characterization of monoclonal antibodies against human airway mucins

The objective of this study was to generate and characterize monoclonal antibodies (MAbs) against human airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins in various physiological or pathological situations of human airway. As an antigen, we used a high molecular mass mucin preparation purified from the sputum of normal human subjects. Two monoclonal hybridomas, namely MAbs HM02 and HM03 were obtained and they showed strong immunoreactivity against purified or crude mucin in sputum or bronchial washing of normal human subject. With the high immunoreactivity of these MAbs, mucin contents could be analyzed with more than 100-fold dilution of human airway secretion. The antibodies recognized carbohydrate epitopes because their immunoreactivity was completely abolished by treatment of the mucin with 5 mM periodate. Further characterization of MAbs HM02 and HM03 showed that: (1) they belong to the IgM type; (2) they bind to high molecular mass mucins based on Western blot; (3) they could indirectly immunoprecipitate human airway mucin and as we know, this is the first to demonstrate immunoprecipitation of human airway mucin with anti-human mucin antibodies; and (4) they bind to the goblet cell in airway epithelium as well as some submucosal glands based on immunohistochemistry. Therefore, MAbs HM02 and HM03 should be able to serve as an invaluable tool in studying the regulation of airway mucins in various physiological and pathological situations of human airway.     

Technology development in breath microanalysis for clinical diagnosis

A new generation of breath tests detects trace amounts of endogenous volatile organic compounds (VOCs) present in the breath. The breath microanalysis is potentially fast and convenient. It opens up a new promising area of using the breath test as a noninvasive diagnostic tool for a variety of diseases. Recent developments in microanalysis technology are expected to greatly facilitate the use of the breath test in clinical evaluations and applications, and these developments are described in the present review.     

Spread of bovine herpesvirus type 5 (BHV-5) in the rabbit brain after intranasal inoculation

Following intranasal inoculation of wild-type BHV-5 in rabbits, we studied the sequential transneuronal passage of the virus in the CNS by immunocytochemistry, histopathology, and virus isolation. At 4 and 6 days postinfection (d.p.i.), rabbits had no or mild neurological signs, and virus was isolated only from the olfactory bulbs. At 8 and 9 d.p.i., infected rabbits had severe neurological signs, and virus could be isolated from multiple regions of the brain segments. In these rabbits, high titers of virus were consistently present in the anterior and posterior cortices, including frontal, piriform/entorhinal, temporal, parietal, and occipital cortices, the hippocampus and the amygdala. Virus was isolated occasionally from the midbrain/diencephalon and pons/medulla. Virus was not isolated from the cerebellum and trigeminal ganglion of rabbits examined from 2-12 d.p.i. Immunocytochemistry revealed virus-specific antigens at 4 d.p.i. within the glomerular layer, external plexiform layer, and mitral cell layer of the main olfactory bulb. At 6 d.p.i., virus-specific antigens were also present within the inner granular layer of the main olfactory bulb. At 8 and 9 d.p.i., widespread BHV-5-specific staining occurred in the areas of the brain connected to the main olfactory bulb, including the frontal/cingulate cortex, anterior olfactory nucleus, lateral olfactory tubercle, piriform/entorhinal cortex, hippocampus, amygdala, dorsal raphe, and locus coeruleus. In the trigeminal ganglion, specific staining was detected within a few neurons at 2,4, 6, 8 d.p.i. However, further spread of the virus along the trigeminal pathway was not evident. These data indicate that BHV-5 replicates and spreads preferentially in the olfactory pathway following intranasal instillation and that this viral spread correlated with the severity of neurological symptoms and histopathological lesions.     

Short-term effects of a new intravascular nitinol stent in canine arteries

RATIONALE AND OBJECTIVES: To evaluate the short-term effects of a new nitinol stent on canine arteries. METHODS: Eighteen nitinol mesh stents were placed in abdominal aortas, common iliac arteries, and renal arteries of six dogs. Angiography was performed to evaluate the patency rates and structural changes of arteries at 1 day, 3 weeks, 4 weeks, and 10 weeks after stent insertion. Gross and light microscopic examinations were performed after angiography. RESULTS: On angiography, the patency rate was 100%, and no thrombosis was observed. All side branches from stented segments were patent. The mean neointimal thickness over and between stent wires was 94 and 167 microns. No difference was found between the aorta and the small vessels. Histologically, the neointima was covered with endothelium and was composed of subintimal fibrosis with mild inflammation. CONCLUSIONS: The new type of nitinol mesh stent showed a high patency rate, with no thrombosis and relatively thin neointimal proliferation.     

Correlation between the degree of contrast enhancement and the volume of peritumoral edema in meningiomas and malignant gliomas

Peritumoral edema and contrast enhancement of brain tumors are both thought to be due to breakdown of the blood-brain barrier (BBB); however, the exact mechanism by which these two phenomena occur and whether there is a quantitative or etiological relationship is not known. Our purpose was to determine whether the relationship between the breakdown of the BBB, defined radiologically as the degree of contrast enhancement, and the volume of surrounding edema is different for high-grade gliomas and meningiomas. We analyzed 13 meningiomas and 23 gliomas. A direct linear relationship between the degree of contrast enhancement (dC) and volume of peritumoral edema (V) with a high correlation coefficient (R = 0.66, P = 0.0006) was established for gliomas. A mathematical relationship between dC and V could not be established for meningioma. The findings for gliomas offer indirect radiological evidence that the defect in the BBB which causes edema is quantitatively and etiologically related to the defect in the BBB responsible for contrast enhancement. For meningiomas, the lack of a relationship between dC and V implies either that the mechanisms responsible for formation of edema and contrast enhancement are fundamentally different or that a physical barrier in certain meningiomas limits propagation of edema into the adjacent white matter. Received: 4 March 1999 Accepted: 18 March 1999